Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000654586 | SCV000776480 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 360 of the RET protein (p.Arg360Gln). This variant is present in population databases (rs762472027, gnomAD 0.006%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 22174939). ClinVar contains an entry for this variant (Variation ID: 543747). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002422430 | SCV002725062 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-01 | criteria provided, single submitter | clinical testing | The p.R360Q variant (also known as c.1079G>A), located in coding exon 6 of the RET gene, results from a G to A substitution at nucleotide position 1079. The arginine at codon 360 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003465422 | SCV004206694 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2023-07-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004702256 | SCV005201971 | uncertain significance | not provided | 2024-03-04 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in an individual with Hirschsprung disease (PMID: 22174939); This variant is associated with the following publications: (PMID: 14633923, Huret2020[article], 26986070, 29538669, 22174939) |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004702256 | SCV005623054 | uncertain significance | not provided | 2024-01-23 | criteria provided, single submitter | clinical testing |